Background Salmonella belongs to the Enterobacteriaceae family, a gram-negative, non-spore-forming, rod-shaped, motile, and pathogenic bacteria that transmit through unhygienic conditions. It is estimated that 21 million new infections arise every year, resulting in approximately 200,000 deaths. It is more prevalent among children, the old aged, and immunocompromised individuals. The frequent usage of classical antimicrobials has begun the increasing emergence of various drug-resistant pathogenic bacterial strains. Hence, this study was intended to evaluate the bioactive seaweed sulfated polysaccharides (SSPs) against the ompF (outer membrane porin F) protein target of Salmonella typhi. SSP is the sulfated compound with a wide range of biological activities, such as anti-microbial, anti-allergy, anti-cancer, anti-coagulant, anti-inflammation, anti-oxidant, and anti-viral. Results In this study, eleven compounds were targeted against S. typhi OmpF by the molecular docking approach and were compared with two commercially available typhoid medications. The SSP showed good binding affinity compared to commercial drugs, particularly carrageenan/MIV-150, carrageenan lambda, fucoidan, and 3-phenyllactate, ranked as top antagonists against OmpF. Further, pharmacokinetics and toxicology (ADMET) studies corroborated that SSP possessed drug-likeness and highly progressed in all parameters. Conclusions AutoDockTools and Schrodinger's QikProp module results suggest that SSP could be a promising drug for extensively drug-resistant (XDR) S. typhi. To the best of our knowledge, this is the first report on in silico analysis of SSP against S. typhi OmpF, thus implying the capabilities of SSPs especially compounds like carrageenans, as a potential anti-microbial agent against Salmonella typhi infections. Eventually, advanced studies could corroborate SSPs to the next level of application in the crisis of XDR microbial diseases. Graphical Abstract